Among the many examples of ectopic hormone production by tumors, the gonadotropin (HCG)-producing neoplasms may represent a unique phenomenon of tumor retro-differentiation. Previous studies have shown these tumors to make not only HCG and/or its alpha and beta fragments, but also to elaborate somatomammotropin and placental alkaline phosphatase. These tumors thus appear to have de-differentiated to perform the same biochemical functions of normal placenta and trophoblastic neoplasms. Previous studies from our laboratory have shown that normal placenta and trophoblastic tumors are capable of aromatizing circulating androgens, particularly, dehydroepiandrosterone sulfate, to estradiol. Since this steroid transformation cannot be demonstrated in normal (non-pregnant) states, elevated estradiol production from this pathway can serve as a useful biochemical marker of trophoblastic neoplasms. We have also studied estrogen production rates and DHEA-SO4 conversion to E2 in patients with ectopic HCG-producing neoplasms and found these elevated. Thus, we feel that ectopic estradiol production by tumor tissue represents another biochemical feature that characterizes functioning trophoblastic tissue, suggesting that these tumors represent an unusual form of tissue retro-differentiation. In the current proposal, we wish to examine estradiol production rates as well as other trophoblastic markers in cancer patients found to have ectopic HCGbeta fragments in their serum. We hope to demonstrate that these neoplasms producing HCGbeta also perform other biochemical functions characteristic of trophoblastic tissue and thus represent an unusual syndrome vs. other ectopic hormonal syndromes where only a single repressed protein and/or its fragments are made by the tumor tissue.